Laboratory Issues

Although numerous reports have confirmed that alterations in EYA1 cause BOR syndrome,66 70 in many of these reports only 20% of affected patients have confirmed EYA1 mutations.81 To explain this low mutation detection rate, some investigators have hypothesized that mutations in another gene tightly linked to EYA1 also cause BOR syndrome. However, using Southern analysis, other investigators have been able to detect mutations in families linked to chromosome 8, in which SSCP analysis and direct sequencing fail to detect EYA1 mutations.81 This finding underscores the major drawback of many PCR-based mutation detection procedures in the study of an autosomal dominant disorder, the inevitable amplification of the normal allele that can mask deleted or disrupted exons.